EP2558156B1 - Device for preparing dilute disinfectant solution - Google Patents
Device for preparing dilute disinfectant solution Download PDFInfo
- Publication number
- EP2558156B1 EP2558156B1 EP11716993.8A EP11716993A EP2558156B1 EP 2558156 B1 EP2558156 B1 EP 2558156B1 EP 11716993 A EP11716993 A EP 11716993A EP 2558156 B1 EP2558156 B1 EP 2558156B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- disinfectant
- reservoir
- dilutant
- solution
- predetermined amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000645 desinfectant Substances 0.000 title claims description 268
- 239000000243 solution Substances 0.000 claims description 244
- 238000007599 discharging Methods 0.000 claims description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 53
- 238000002156 mixing Methods 0.000 claims description 45
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 41
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 39
- 239000012528 membrane Substances 0.000 claims description 33
- 239000012895 dilution Substances 0.000 claims description 27
- 238000010790 dilution Methods 0.000 claims description 27
- 230000007246 mechanism Effects 0.000 claims description 17
- 206010052428 Wound Diseases 0.000 claims description 16
- 208000027418 Wounds and injury Diseases 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 11
- 230000009471 action Effects 0.000 claims description 10
- 230000015556 catabolic process Effects 0.000 claims description 5
- 238000006731 degradation reaction Methods 0.000 claims description 5
- 239000000796 flavoring agent Substances 0.000 claims description 5
- 235000019634 flavors Nutrition 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims 1
- 239000000975 dye Substances 0.000 description 37
- 239000000203 mixture Substances 0.000 description 20
- 239000012530 fluid Substances 0.000 description 19
- 238000005086 pumping Methods 0.000 description 19
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000007788 liquid Substances 0.000 description 14
- 230000004913 activation Effects 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 238000001356 surgical procedure Methods 0.000 description 11
- 230000008859 change Effects 0.000 description 10
- 239000011259 mixed solution Substances 0.000 description 9
- 239000002324 mouth wash Substances 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000005484 gravity Effects 0.000 description 5
- 229940113601 irrigation solution Drugs 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000000049 pigment Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZXJXZNDDNMQXFV-UHFFFAOYSA-M crystal violet Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1[C+](C=1C=CC(=CC=1)N(C)C)C1=CC=C(N(C)C)C=C1 ZXJXZNDDNMQXFV-UHFFFAOYSA-M 0.000 description 3
- 230000003292 diminished effect Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229960001235 gentian violet Drugs 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- YYGBVRCTHASBKD-UHFFFAOYSA-M methylene green Chemical compound [Cl-].C1=CC(N(C)C)=C([N+]([O-])=O)C2=[S+]C3=CC(N(C)C)=CC=C3N=C21 YYGBVRCTHASBKD-UHFFFAOYSA-M 0.000 description 3
- 229960000907 methylthioninium chloride Drugs 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- MHOFGBJTSNWTDT-UHFFFAOYSA-M 2-[n-ethyl-4-[(6-methoxy-3-methyl-1,3-benzothiazol-3-ium-2-yl)diazenyl]anilino]ethanol;methyl sulfate Chemical compound COS([O-])(=O)=O.C1=CC(N(CCO)CC)=CC=C1N=NC1=[N+](C)C2=CC=C(OC)C=C2S1 MHOFGBJTSNWTDT-UHFFFAOYSA-M 0.000 description 2
- VZCCTDLWCKUBGD-UHFFFAOYSA-N 8-[[4-(dimethylamino)phenyl]diazenyl]-10-phenylphenazin-10-ium-2-amine;chloride Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1N=NC1=CC=C(N=C2C(C=C(N)C=C2)=[N+]2C=3C=CC=CC=3)C2=C1 VZCCTDLWCKUBGD-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229910019093 NaOCl Inorganic materials 0.000 description 2
- 206010067482 No adverse event Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 208000002847 Surgical Wound Diseases 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- WLKAMFOFXYCYDK-UHFFFAOYSA-N [5-amino-4-[[3-[(2-amino-4-azaniumyl-5-methylphenyl)diazenyl]-4-methylphenyl]diazenyl]-2-methylphenyl]azanium;dichloride Chemical compound [Cl-].[Cl-].CC1=CC=C(N=NC=2C(=CC([NH3+])=C(C)C=2)N)C=C1N=NC1=CC(C)=C([NH3+])C=C1N WLKAMFOFXYCYDK-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 description 2
- 230000000994 depressogenic effect Effects 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 229960002143 fluorescein Drugs 0.000 description 2
- 239000013505 freshwater Substances 0.000 description 2
- 229960004657 indocyanine green Drugs 0.000 description 2
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 2
- RBDJQFKUZPMOFH-UHFFFAOYSA-I pentasodium;3-amino-4-[[4-[4-[(2-amino-3,6-disulfonatonaphthalen-1-yl)diazenyl]-3-sulfonatophenyl]phenyl]diazenyl]naphthalene-2,7-disulfonate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(N)=C1N=NC1=CC=C(C=2C=C(C(N=NC=3C4=CC=C(C=C4C=C(C=3N)S([O-])(=O)=O)S([O-])(=O)=O)=CC=2)S([O-])(=O)=O)C=C1 RBDJQFKUZPMOFH-UHFFFAOYSA-I 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 239000012780 transparent material Substances 0.000 description 2
- PQMFVUNERGGBPG-UHFFFAOYSA-N (6-bromopyridin-2-yl)hydrazine Chemical compound NNC1=CC=CC(Br)=N1 PQMFVUNERGGBPG-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- 208000023329 Gun shot wound Diseases 0.000 description 1
- 206010029803 Nosocomial infection Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 239000013010 irrigating solution Substances 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
- A01N59/08—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/10—Bag-type containers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/18—Arrangements for indicating condition of container contents, e.g. sterile condition
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2093—Containers having several compartments for products to be mixed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J7/00—Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine
- A61J7/0015—Devices specially adapted for taking medicines
- A61J7/0046—Cups, bottles or bags
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/22—Phase substances, e.g. smokes, aerosols or sprayed or atomised substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/006—Sprayers or atomisers specially adapted for therapeutic purposes operated by applying mechanical pressure to the liquid to be sprayed or atomised
- A61M11/007—Syringe-type or piston-type sprayers or atomisers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M35/00—Devices for applying media, e.g. remedies, on the human body
- A61M35/003—Portable hand-held applicators having means for dispensing or spreading integral media
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
- A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/19—Syringes having more than one chamber, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M35/00—Devices for applying media, e.g. remedies, on the human body
Definitions
- the invention relates to a device for preparing a dilute disinfectant solution, for example, a dilute solution of stabilised sodium hypochlorite solution.
- the present applicant has recognised that such dilute disinfectant solutions degrade over time and thus need to be mixed when required. Furthermore, the present applicant has recognised that said solutions need to be recognised as fresh via use of an indicator and they need to be delivered to the site of need via a sterile delivery device that is simple to use, especially in clinical applications including within medicine, dentistry and veterinary surgery.
- US 5,391,351 discloses a device for the preparation for disposal of non-gaseous body waste fluids.
- the device comprises various compartments which separately contain the body waste fluids to be disposed of, a disinfectant powder for deactivation of infectious agents contained within the body waste fluids, and a xerogel composition for solidification of the body waste fluids.
- the dilute disinfectant solution can be mixed when needed.
- the mixing is simple and quick for the user but still done in a clinically acceptable manner.
- the proposed devices are preferably cheap to manufacture and in some embodiments sterilizable and disposable to prevent contamination.
- the device comprises an indicator (or second) reservoir for an indicator indicating the activity of the dilute disinfectant solution.
- the indicator reservoir may be a separate reservoir and the device may further comprise indicator discharging means for discharging a predetermined amount of said indicator from said second reservoir to be mixed with said predetermined amount of dilutant and said predetermined amount of undiluted disinfectant solution.
- the indicator reservoir may be integral with either the disinfectant reservoir or the dilutant reservoir.
- the indicator may be pre-mixed with the undiluted disinfectant solution in the disinfectant reservoir or pre-mixed with the dilutant in the dilutant reservoir.
- the indicator may be formed from the combination of components contained partly in the dilutant reservoir and partly in the disinfectant reservoir. In this case, the disinfectant and/or dilutant discharging means provide the indicator discharging means.
- the device is capable of providing a disinfectant composition comprising dilute stabilised sodium hypochlorite solution and an indicator to show that the dilute sodium hypochlorite solution is fresh and active.
- the device is capable of providing a pharmaceutically acceptable composition comprising dilute stabilised sodium hypochlorite solution and an indicator to show that the dilute sodium hypochlorite solution is fresh and active.
- the pharmaceutically acceptable composition may further comprise a pharmaceutically acceptable dilutant or carrier.
- the pharmaceutically acceptable composition may be used in medicine, in particular for preventing infection and aiding healing.
- the dilute disinfectant solution can be used in the manufacture of the pharmaceutically acceptable composition for use in preventing infection. It can also be used in a method of treating infection in a mammal comprising administering an effective amount of the composition defined above to said mammal.
- the predetermined amount of dilutant and the predetermined amount of undiluted disinfectant solution are determined so as to provide the desired dilution of the stabilised disinfectant solution.
- the dilutant may be water.
- the undiluted disinfectant solution in the first reservoir may be a stabilised sodium hypochlorite solution at 1% or 2% sodium hypochlorite, e.g. a disinfectant known as "Milton's Solution” comprising sodium chloride.
- the dilute disinfectant solution may be a 2.5% - 10% solution of Milton's solution diluted in water where the undiluted disinfectant solution is 2% sodium hypochlorite.
- the sodium chloride in said solution is typically at a concentration of 16.5%.
- the ratio of predetermined amount of undiluted disinfectant solution to predetermined amount of water may be in the range between 1 to 10 to 1 to 40.
- the dilute disinfectant solution may be a 5% to 20% solution of Milton's solution diluted in water where the undiluted disinfectant solution is 1% sodium hypochlorite.
- ratio of the predetermined amount of undiluted disinfectant solution to predetermined amount of water to may be in the range between 1 to 5 to 1 to 20.
- the predetermined amount of water and the predetermined amount of undiluted disinfectant solution may be such that the dilute disinfectant solution may be a buffered sodium hypochlorite solution where the sodium hypochlorite is in a concentration range of 0.025% - 0.2%, preferably 0.05% - 0.1%.
- the buffering of the sodium hypochlorite solution can provide stabilisation of the dilute disinfectant solution.
- the dilute disinfectant solution may be used as a disinfectant solution for use as an irrigating solution for surgical sites or wounds.
- the solution can also be used for a mouth rinse after oral surgery, dental surgery or following oral hygiene procedures.
- a portable device for mixing a dilute disinfectant solution to be used as a mouth rinse comprising a first reservoir for undiluted disinfectant solution, a second reservoir for an indicator indicating the activity of the dilute disinfectant solution, a chamber which comprises indication means to indicate to a user the amount of water to be added to the chamber and which is connected to said first and second reservoirs, means for discharging a predetermined amount of said undiluted disinfectant solution from said first reservoir into said chamber and means for discharging a predetermined amount of said indicator from said second reservoir into said chamber, wherein said predetermined amounts of said undiluted disinfectant solution and said indicator are mixed with a predetermined amount of water in said chamber to provide the dilute disinfectant solution.
- the indicator indicates the activity of the dilute disinfectant solution, in other words, the indicator shows the dilute disinfectant solution is fresh and active.
- the indicator is not the active ingredient of the dilute disinfectant solution.
- the indicator preferably degrades over time when mixed with the dilute disinfectant solution. In other words, the indicator preferably does not degrade over time when mixed with either neat dilutant or neat disinfectant.
- the indicator may be included in either the dilutant or disinfectant reservoir rather than in a separate reservoir.
- the indicator may comprise a first component which shows the dilute disinfectant solution is fresh and active and a second component which degrades the first component.
- the first and second components may be incorporated one in the dilutant reservoir and one in the disinfectant reservoir. Alternatively, two additional reservoirs may be included.
- the indicator (e.g. first component) may be a dye or a flavour or combination thereof (e.g. in a mouthwash).
- the indicator preferably produces a noticeable change over time to a user of the dilute disinfectant solution.
- a dye there is either a significant colour change or the solution becomes colourless.
- a flavour there is a noticeable degradation of the flavouring such that the solution becomes unpalatable. Since the resultant solution is most effective, if diluted immediately prior to use, the noticeable change may occur within a time frame of 45 minutes to 1 hour. In this time frame, the noticeable change occurs prior to the loss of therapeutic action of dilute disinfectant solution.
- the dye may be a dye such as those which are routinely used in surgical procedures with no adverse effects.
- suitable dyes include azafloxin, basic blue (nil blue sulphate), bismarck brown, basic red (rhodamine 6G), bengal red, brilliant crysyl blue, eosin, fluorescein, gentian violet, indocyanine green, janus green, methylene green, methylene blue, neutral red, trypan blue, and trypan red.
- the predetermined amount of dye is preferably low enough to prevent interaction with active components but great enough so that the dye colour is visible within the dilute disinfectant solution.
- the indicator may be organic or inorganic, biocompatible, non-toxic and pharamaceutically acceptable.
- the indicator (preferably a dye) may indicate the strength or dilution of the disinfectant. For example, if the undiluted disinfectant solution is diluted by ten (1 part undiluted disinfectant solution in 10 parts of water) then the indicator dye would be blue. If the dilution is diluted by 20 (1 part of undiluted disinfectant solution in 20 parts of water) the indicator would be green. If the undiluted disinfectant solution is diluted by 30 (1 part undiluted disinfectant solution in 30 parts of water) then the indicator dye would be orange. If the undiluted disinfectant solution is diluted by 40 (1 part undiluted disinfectant solution in 40 of water) then the indicator dye would be red. In such an aspect, the indicator dye may preferably be packaged with the specific dilution.
- the indicator may also show that the disinfectant is at the correct dilution.
- the indicator may be an organic or inorganic dye which can be degraded by the chemical action of the disinfectant, e.g. the innate oxidative capacity of the hypochlorite disinfectant.
- the indicator may suffer a diminishment of intensity over a period of 1 hour. This indicates the activity of the disinfectant is not sufficiently reliable to produce the clinical action desired.
- the indicator is selected so that it degrades and shows a change in property over the same period in which the activity of the chosen dilution of said disinfectant degrades.
- one dye might change from coloured to colourless over 30 minutes, while another might make this change over 1 hour while another might take 2 hours. This might be useful for different dilutions of disinfectant where the concentration is critical, e.g. in surgical situations such as the disinfecting of dirty wounds, gunshot wounds or a slower trickle irrigation of a surgical site that is uncontaminated.
- the colour degradation of the indicator dye may be used as an indicator of the reduction in activity of the disinfectant.
- the intensity of the colour can be measured by comparison to a set colour charts or with a calibrated optical measuring device to indicate disinfectant activity.
- the dilute disinfectant can have an indicator such as a dye added after its dilution to indicate continued activity.
- the dilute disinfectant e.g. Milton's number 2 solution diluted with water
- the indicator may be an indicator dye which is an unstable compound which spontaneously degrades over a period of time (preferably from 30 minutes to 2 hours, e.g. over 30 minutes, 45 minutes, 1 hour or 2 hours).
- the indicator is preferably formed at the time of dilution of the undiluted disinfectant solution by adding two separate components together in order to generate the indicator dye. Once generated it is then added to the dilute disinfectant solution, after which the indicator dye "degrades" from exhibiting colour (e.g. red, blue or green) to being colourless.
- the dilutant, undiluted disinfectant solution and indicator may be simultaneously mixed or the dilutant and undiluted disinfectant solution mixed first with the indicator discharging means arranged to discharge the indicator into the dilute disinfectant.
- the volume of dilute disinfectant solution provided by the device may be 1 litre.
- the predetermined amount of dilutant may be 945ml of water and the predetermined amount of disinfectant may be 50ml of Milton 2% (i.e. 2% hypochlorite in 16.5% sodium chloride).
- the predetermined amount of indicator may be 5ml of methylene blue.
- the dilute disinfectant solution has 94.5% dilutant, 5% disinfectant and 0.5% indicator.
- the freshly mixed solution is blue. After 30 minutes, the solution is blue with diminished hue and after 1 hour the colour is virtually absent.
- the volume of dilute disinfectant solution provided by the device may be 1 litre.
- the predetermined amount of dilutant may be 880ml of water and the predetermined amount of undiluted disinfectant solution may be 100ml of Milton 2% (i.e. 2% hypochlorite in 16.5% sodium chloride).
- the predetermined amount of indicator may be 20ml of methylene green.
- the dilute disinfectant solution has 88% dilutant, 10% undiluted disinfectant solution and 2% indicator. In this case, the freshly mixed solution is green. After 30 minutes, the solution is green with diminished hue and after 1 hour the colour is virtually absent.
- the volume of dilute disinfectant solution provided by the device may be 1 litre.
- the predetermined amount of dilutant may be 970ml of water and the predetermined amount of undiluted disinfectant solution may be 25ml of Milton 2% (i.e. 2% hypochlorite in 16.5% sodium chloride).
- the predetermined amount of indicator may be 5ml of gentian violet.
- the dilute disinfectant solution has 97% dilutant, 2.5% undiluted disinfectant solution and 0.5% indicator.
- the freshly mixed solution is violet. After 30 minutes, the solution is violet with diminished hue and after 1 hour the colour is virtually absent.
- the diminishing hue indicates that the dye is being degraded at a rate that approximates the gradual reduction in concentration of the active hypochlorite. After 1 hour, there may be active hypochlorite present but it is not verifiably adequate to guarantee full clinical efficacy.
- the indicator thus acts as a safeguard to ensure the solution is used within a time period where the therapeutic concentration is maintained and that it is also withheld once the colour intensity indicates inadequate levels of active hypochlorite. It will be appreciated that several alternative combinations of indicator dyes and dilutant may be used and the examples given above are not exhaustive nor restrictive.
- a dilute disinfectant solution that can be prepared is a buffered dilute sodium hypochlorite solution, wherein said dilute stabilised sodium hypochlorite solution is buffered to a pH of from 5-10, preferably 6-8.
- the buffer may be any buffer suitable to maintain the pH of the dilute solution at the desired pH and, if the solution is to be used pharmacologically, then it must be pharmaceutically acceptable.
- suitable buffers for use include buffers selected from the group consisting of a phosphate/phosphoric acid buffer, a borate/boric acid buffer, a citrate/citric acid buffer and a citrate/citric acid buffer.
- Dilute sodium hypochlorite solutions such as dilute Milton's solutions 1 and 2 typically also include a stabiliser such as sodium chloride.
- the disinfectant reservoir is preferably opaque to prevent degradation of the undiluted disinfectant solution due to light exposure.
- a device for mixing a dilute disinfectant solution comprising a first reservoir for said undiluted disinfectant solution, a chamber connected to said first reservoir and means for discharging a predetermined amount of said undiluted disinfectant solution from said first reservoir into said chamber, wherein said predetermined amount of said undiluted disinfectant solution is mixed with a predetermined amount of dilutant in said chamber to provide the dilute disinfectant solution and wherein said first reservoir is configured to prevent the disinfectant solution therein being exposed to light.
- the first reservoir may have opaque walls.
- the predetermined amounts of undiluted disinfectant solution and dilutant may be as described above.
- a second reservoir of indicator may be added to the device as described above. The aspects of the invention may thus be combined.
- the device may be arranged to prevent dispensing neat disinfectant.
- Dispensing neat disinfectant may be dangerous because of the acute short term irritation and also long term because undiluted disinfectant does not degrade.
- the device may comprise an outlet for the dilute disinfectant and there may be no direct access from the disinfectant reservoir to the outlet.
- the indicator discharging means and/or the disinfectant discharging means may be arranged to discharge said indicator and/or said undiluted disinfectant solution into said chamber. The dilute disinfectant may then be provided from the chamber which is connected to the outlet.
- the device may also be arranged to prevent dispensing neat dilutant. This is dangerous in the sense that the clinician is using dilutant rather than dilute disinfectant solution and thus not obtaining the clinical benefit.
- the device may be provided with a mechanism (e.g. locking mechanism) which prevents the device providing a discharge, e.g. a discharge of neat disinfectant and/or a discharge of neat dilutant.
- a mechanism e.g. locking mechanism
- the locking mechanism preferably prevents discharging from an outlet of the device before mixing the dilute disinfectant.
- the locking mechanism may be in the form of a friable seal which may only be broken after mixing.
- the disinfectant reservoir may hold only said predetermined amount of said undiluted disinfectant solution.
- said disinfectant discharging means is preferably arranged to wholly and completely discharge said predetermined amount of said undiluted disinfectant solution from said disinfectant reservoir.
- the indicator reservoir may hold only said predetermined amount of said indicator and/or said indicator discharging means may be arranged to wholly and completely discharge said predetermined amount of said indicator from said indicator reservoir.
- the chamber may be a dilutant reservoir holding only said predetermined amount of dilutant.
- portable device for mixing a dilute disinfectant solution comprising a first reservoir comprising a predetermined amount of undiluted disinfectant solution, a chamber which is connected to said first reservoir and which holds a predetermined amount of dilutant, means for discharging said predetermined amount of said undiluted disinfectant solution from said first reservoir into said chamber to be mixed with said predetermined amount of dilutant in said chamber wherein said device provides the dilute disinfectant solution at a fixed dilution determined by the ratio of the predetermined amount of said undiluted disinfectant solution to the predetermined amount of dilutant, and an indicator reservoir holding an indicator indicating the activity of the dilute disinfectant solution.
- the predetermined amount of said undiluted disinfectant solution is preferably wholly and completely discharged into the predetermined amount of dilutant. Since the dilutant and disinfectant reservoirs hold only the predetermined amounts of dilutant and undiluted disinfectant solution, once they are mixed, the device has been used. In other words, the device may only be used once, then it is discarded. The device is thus a single use or one-off use device.
- the device may further comprise dilutant discharging means for discharging said predetermined amount of dilutant, the dilutant discharging means being arranged to simultaneously discharge said predetermined amount of dilutant from said chamber as said disinfectant discharging means discharges said predetermined amount of undiluted disinfectant solution whereby said undiluted disinfectant solution is mixed with said dilutant as the device provides the dilute disinfectant solution.
- the liquids are simultaneously dispensed with mixing occurring at the point of dispensing.
- the dilutant reservoir may hold only the predetermined amount of dilutant and the disinfectant reservoir may hold only the predetermined amount of undiluted disinfectant solution and both predetermined amounts may be discharged wholly and completely on activation. Thus, in this way, the device may only be used once, then it is discarded.
- the device may further comprise a dilutant reservoir for dilutant which is connected to the chamber and dilutant discharging means for discharging said predetermined amount of dilutant from said dilutant reservoir into said chamber.
- the dilutant reservoir may be connected to the chamber via an additional dilutant reservoir which holds the predetermined amount of dilutant.
- the disinfectant reservoir may be connected to the chamber via an additional disinfectant reservoir which holds the predetermined amount of undiluted disinfectant solution. Either or both of the additional disinfectant reservoir and additional dilutant reservoir may be integral with the chamber. In these arrangements, more than one dose of diluted disinfectant may be dispensed from the device.
- the dilutant and/or disinfectant discharging means may be in the form of a pumping mechanism which draws dilutant and/or undiluted disinfectant solution from the main reservoirs into the additional reservoirs.
- the pumping mechanism may comprise a single pump which draws dilutant and undiluted disinfectant solution from the main reservoirs into the additional reservoirs during a singe stroke. In this case, the portions of the single stroke during which the additional reservoirs draw from the main reservoirs determines the mixing ratio.
- the pumping mechanism may comprise two or more pumps arranged to work synchronously, each one drawing fluid from each reservoir simultaneously. The drawn fluid passes into a common outlet or a set of closely spaced outlets. In this case, the ratio of the pumping volume per stroke sets the desired mixing ratio of the two fluids.
- the pump(s) may be positive displacement plunger pumps.
- the chamber is a dilutant reservoir which comprises indication means to indicate to a user the amount of dilutant to be added to the reservoir, e.g. the chamber is in the form of a cup and the device delivers dilute disinfectant solution is to be used as a mouth rinse.
- the means for discharging the predetermined amounts of undiluted disinfectant solution, dilutant and/or indicator may be a pump.
- the pump may be manually controlled, e.g. by depression of a button.
- the means may be in the form of a syringe or similar device which is manually discharged into the chamber.
- the means may be in the form of a twist or push activation mechanism.
- the means may be a friable membrane which is ruptured by a user (e.g. following activation of the twist or push mechanism) to discharge said predetermined amount of said undiluted disinfectant solution.
- the device may be configured such that opening of the device initiates the discharging of any one or all of the predetermined amounts of undiluted disinfectant solution, dilutant and/or indicator.
- the device may be in the form of a drip bag.
- the main body of the drip bag may be the dilutant reservoir which may hold dilutant in the range 250ml to 2 litres.
- the disinfectant reservoir and the indicator reservoir may be mounted externally or internally to the dilutant reservoir.
- the disinfectant discharging means and the indicator discharging means (where used) may be arranged to wholly and completely discharge the undiluted disinfectant solution and indicator into the dilutant reservoir.
- the disinfectant discharging means and the indicator discharging means may be in the form of syringes or friable seals which are broken on activation, e.g. by twist or push.
- the device may be in the form of a bottle.
- the main body of the bottle may be the dilutant reservoir which may hold dilutant in the range 0.1 litre to 2 litres.
- the disinfectant reservoir and the indicator reservoir may be mounted to the dilutant reservoir, e.g. on the side on the bottle, in the bottle lid or within the bottle.
- the disinfectant discharging means and the indicator discharging means (where used) may be arranged to wholly and completely discharge the undiluted disinfectant solution and indicator into the dilutant reservoir.
- the predetermined amounts of undiluted disinfectant solution, dilutant and/or indicator may be drawn from the respective reservoirs which hold a greater amount of the undiluted disinfectant solution, dilutant and/or indicator.
- the disinfectant discharging means and the indicator discharging means may be in the form of pumps or friable seals which are broken on activation.
- the device is capable of providing a dilute disinfectant solution which may be used for the following:
- Figure 1 shows a first device 100 which produces a given quantity of freshly constituted "Hypo-Stream" solution for use as a surgical disinfectant and irrigation solution.
- the device 100 functions like a conventional pump action spray bottle delivering the correctly constituted solution as a spray via an integral nozzle at one end.
- the device 100 comprises three reservoirs (122, 124, 126).
- the first (or disinfectant) reservoir 122 (Chamber A) comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2. This reservoir is opaque.
- the second (or indicator) reservoir 124 (Chamber B) holds an organic biocompatible and non-toxic dye.
- the third (or dilutant) reservoir 126 (Chamber C) comprises a chamber of sterile pure water at a pre-determined volume between 0.1 and 2 litres.
- the chamber has an outlet 142 in the form of a spray nozzle at the opposed end of the bottle to the first and second reservoirs.
- the outlet 142 may be industry standard or system specific. The outlet allows delivery of the correctly mixed dilute solution into a surgical wound or site as indicated in the direction of the arrow.
- the first and second reservoirs could be incorporated in the lid, along with the dispensing outlet (see e.g. Figure 4 ).
- the first and second reservoirs 122, 124 are attached to the outer wall of the third reservoir 126 to form an integral unit.
- the first and second reservoirs 122, 124 are situated either within the third reservoir or on the outside of the third reservoir (as shown).
- the first and second reservoirs 122, 124 comprise a mechanism (i.e. a disinfectant discharging means and an indicator discharging means) which is configured to allow the liquids in these reservoirs to be introduced wholly and completely into the water in the third reservoir 126.
- a mechanism i.e. a disinfectant discharging means and an indicator discharging means
- activation i.e. mixing
- Activation is also a binary process (i.e. partial mixing is impossible).
- the third reservoir thus acts as the holding chamber for mixing the three fluids together. Furthermore, since the dilutant reservoir is positioned between the outlet and the disinfectant and indicator reservoirs, the device can only discharge diluted disinfectant or dilutant. In other words, dispensing neat disinfectant is impossible because the disinfectant reservoir has no direct access to the dispensing outlet.
- the relative volumes of liquid in the three reservoirs is such that the final mixed solution is the desired "Hypo-Stream” solution.
- This solution can be delivered by pump action to the site of surgery or to a wound.
- the third reservoir 126 may contain pure water at a pre-determined volume between 0.1 and 2 litres.
- the volume of solution within the second reservoir is determined so that when the solution is discharged into the third reservoir, the resultant solution has a dilution in the range of 0.025% sodium hypochlorite to 0.2% sodium hypochlorite).
- Milton 1 solution is diluted in the range of 1 part in 20 parts water to 1 part in 5 parts water.
- the third reservoir comprises 1 litre of water, there must be between 0.05 and 0.2 litres of Milton 1 solution in the first reservoir.
- Milton 2 solution is diluted in the range of 1 part in 40 parts water to 1 part in 10 parts water, i.e.
- the device will result in a set dilution which falls within a range of 1 in 10 - 1 in 40 dilution with pure water, i.e. 0.2% - 0.05% NaOCl.
- the device of Figure 1 is a portable and autonomous device to produce a given quantity of freshly constituted "Hypo-Stream" solution for use as a surgical disinfectant and irrigation solution.
- the device is disposable and not refillable.
- the device consists of a bottle which may be made of a flexible transparent material.
- the pigment is an indicator of fresh mix as the pigment degrades over time.
- the device is designed for use for humans and animals.
- Figure 2 shows an alternative device 200 for delivering a correctly diluted solution known as "hypo-stream" solution for use in surgical or similar situations.
- the device is disposable and not refillable.
- the device 200 functions like a conventional "drip bag” and delivers gravity fed Hypo-Stream solution via conventional or system specific drip bag tubing mechanisms. As in Figure 1 , the device 200 comprises three reservoirs (222, 224, 226).
- the first (or disinfectant) reservoir (Syringe B) comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2. This reservoir is opaque.
- the second reservoir (Syringe C) holds an organic biocompatible and non-toxic dye.
- the third (or dilutant) reservoir (Bag A) comprises a large bag of pure water with an outlet 242 at the bottom allowing attachment to conventional or system specific drip bag tubing.
- the outlet 242 may be an industry standard connector or a connector specifically adapted to the system.
- the first and second reservoirs 222, 224 are attached to the outer wall of the third reservoir 226.
- the first and second reservoirs 222, 224 are situated either within the third reservoir or on the outside of the third reservoir (as shown).
- the first and second reservoirs 222, 224 each comprise a mechanism (i.e. a disinfectant discharging means and an indicator discharging means) which is configured to allow the liquids in these reservoirs to be introduced wholly and completely into the water in the third reservoir.
- the first and second reservoirs may be in the form of syringes which a user may discharge into the third reservoir.
- the third reservoir thus acts as the holding chamber for mixing the three fluids together. As with Figure 1 , the arrangement thus prevents dispensing of neat disinfectant and is a one-way, binary process.
- the relative volumes of liquid in the three reservoirs is such that the final mixed solution is the desired "Hypo-Stream” solution.
- This solution can be delivered under force of gravity and via a drip tubing arrangement to the site of surgery or to a wound.
- the third reservoir 226 may contain pure water at a pre-determined volume between 250ml and 2 litres.
- the volume of solution within the second reservoir is determined so that when the solution is discharged into the third reservoir, the resultant solution has a dilution in the ranges indicated above.
- Milton 1 solution is diluted in the range of 1 part in 20 parts water to 1 part in 5 parts water.
- the third reservoir comprises 1 litre of water, there must be between 0.05 and 0.2 litres of Milton 1 solution in the first reservoir.
- Milton 2 solution is diluted in the range of 1 part in 40 parts water to 1 part in 10 parts water, i.e. for 1 litre of water in the third reservoir, there must be between 0.1 and 0.025 litres of Milton 2 solution.
- the second reservoir is thus pre-filled to ensure the resultant solution has a desired concentration within these ranges.
- Figure 3 shows a third device 300 which produces a given quantity of freshly constituted "Hypo-Stream" solution. This may be for use as a mouth rinse.
- the device 300 comprises three reservoirs 322, 324, 326.
- the first (or disinfectant) reservoir 322 (Pump Chamber B) holds stabilised sodium hypochlorite solution. This reservoir is opaque.
- the second (or indicator) reservoir 324 (Pump Chamber C) contains a flavouring which is organic and biocompatible. The flavour is such that there is a noticeable degradation of the flavouring such that the solution becomes unpalatable. Since the resultant solution is most effective, if diluted immediately prior to use, the noticeable change may occur within a time frame of 45 minutes to 1 hour. In this time frame, the noticeable change occurs prior to the loss of therapeutic action of dilute disinfectant solution.
- the third (or dilutant) reservoir 326 is in the form of a plastic cup (Cup A).
- An indication line 328 is marked on the inside (and/or outside) of the cup to indicate the appropriate level to fill with water.
- the first and second reservoirs 322, 324 are two side-by-side chambers mounted to the top rim of the cup.
- the first and second reservoirs may be considered a "piggy-back" dispenser to add buffered sodium hypochlorite solution and flavouring into the water-filled cup. When the liquids in the first and second chambers are exhausted the device may be discarded and is thus disposable. Alternatively, a new pump dispenser may be attached to the cup.
- Both the first and second reservoirs 322, 324 have disinfectant and indicator discharging means which are activated by a button 330.
- the discharging means may be in the form of pumps or in the form of friable seals. If a pump is used, more than one dose of undiluted disinfectant solution and indicator may be included in the reservoirs. If a friable seal (or bag) is used, the undiluted disinfectant solution and indicator may be wholly and completely discharged.
- the cup is filled with fresh water to the line preferably before (but possibly after) activation of the dispenser. The cup thus acts as the third reservoir and the holding chamber for mixing the liquids.
- the device 300 makes it possible to add the appropriate amount of 1% or 2% buffered sodium hypochlorite solution plus flavouring to a cup of fresh water.
- the line on the cup is set such that when the first reservoir holds Milton 2 solution, a user may activate the pump once to produce a mouth rinse that is 1 part Milton (2) in 40 parts of water (with flavouring).
- a subsequent additional activation of the pump produces a "Hypo-Stream” solution at 1 part Milton (2) in 20 of water.
- the resultant "Hypo-Stream” solution is to be used as a mouth-rinse.
- the device is used over the period in which it takes to exhaust the sodium hypochlorite and flavouring.
- Figure 4 shows a fourth device 400 which produces a given quantity of freshly constituted "Hypo-Stream" solution for use as a surgical disinfectant and irrigation solution.
- the device 400 functions like a conventional washer bottle delivering gravity fed or positive pressure wound wash solution via an integral nozzle or spout at one end.
- the device 400 comprises three reservoirs (422, 424, 426).
- the first (or disinfectant) reservoir 422 (Chamber A) comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2. This reservoir is opaque.
- the second (or indicator) reservoir 424 (Chamber B) holds an organic biocompatible and non-toxic dye.
- the third (or dilutant) reservoir 426 (Chamber C) comprises a chamber of sterile pure water at a pre-determined volume between 0.1 and 2 litres.
- the chamber has an industry standard or system specific outlet 442 in the form of a nozzle or spout at the opposed end of the bottle to the first and second reservoirs.
- the outlet allows delivery of the correctly mixed dilute solution into a surgical wound or site.
- the correctly mixed solution may be gravity fed when the bottle is held vertically or squeezed out of the bottle onto the wound of the animal or human.
- the solution may be poured or sprayed onto the wound.
- the first and second reservoirs 422, 424 are attached to the outer wall of the third reservoir 426 to form an integral unit.
- the first and second reservoirs 422, 424 are situated either within the third reservoir or on the outside of the third reservoir (as shown).
- the first and second reservoirs 422, 424 comprise a mechanism which is configured to allow the liquids in these reservoirs to be introduced wholly and completely into the water in the third reservoir 426.
- there may be a seal between each of the first and second reservoirs and the third reservoir which is opened or punctured by twist or push activation by a user.
- the third reservoir thus acts as the holding chamber for mixing the three fluids together.
- the arrangement thus prevents dispensing of neat disinfectant and is a one-way, binary process.
- the relative volumes of liquid in the three reservoirs is such that the final mixed solution is the desired "Hypo-Stream” solution.
- This solution can be delivered under force of gravity and via an industry standard drip tubing arrangement to the site of surgery or to a wound.
- the third reservoir 426 may contain pure water at a pre-determined volume between 0.1 and 2 litres.
- the volume of solution within the second reservoir is determined so that when the solution is discharged into the third reservoir, the resultant solution has a dilution in the range of 0.05% sodium hypochlorite to 0.2% sodium hypochlorite).
- Milton 1 solution is diluted in the range of 1 part in 20 parts water to 1 part in 5 parts water.
- the third reservoir comprises 1 litre of water, there must be between 0.05 and 0.2 litres of Milton 1 solution in the first reservoir.
- Milton 2 solution is diluted in the range of 1 part in 40 parts water to 1 part in 10 parts water, i.e. for 1 litre of water in the third reservoir, there must be between 0.025 and 0.1 litres of Milton 2 solution.
- the second reservoir is thus pre-filled to ensure the resultant solution has a desired concentration within these ranges.
- the device of Figure 4 is a portable and autonomous device to produce a given quantity of freshly constituted "Hypo-Stream" solution for use as a surgical disinfectant and irrigation solution.
- the device is disposable and not refillable.
- the device consists of a bottle made of a flexible transparent material.
- the pigment is an indicator of fresh mix as the pigment degrades over time.
- the device is designed for use for humans and animals.
- each embodiment delivers either 1 in 10 dilution or 1 in 20 dilution or 1 in 30 dilution or 1 in 40 dilution and the correct dilution can be chosen for the correct application. It is not possible for a user to alter the dilution produced by any of the designs and thus ensuring the correct dilution is delivered each time.
- the dye is such that there is either a significant colour change or the solution becomes colourless within a 45 to 60 minute timeframe.
- the dye may be a dye such as those which are routinely used in surgical procedures with no adverse effects. Examples of suitable dyes include azafloxin, basic blue (nil blue sulphate), bismarck brown, basic red (rhodamine 6G), bengal red, brilliant crysyl blue, eosin, fluorescein, gentian violet, indocyanine green, janus green, methylene green, methylene blue, neutral red, trypan blue, and trypan red.
- the predetermined amount of dye is preferably low enough to prevent interaction with active components but great enough so that the dye colour is visible within the dilute disinfectant solution.
- FIGS 5a and 5b show a fifth device 500 which produces a given quantity of freshly constituted "Hypo-Stream" solution for use as a surgical disinfectant and irrigation solution.
- the device 500 is in the form of a bottle comprising two reservoirs (522 and 524).
- the first (or disinfectant) reservoir 522 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2 and is located in the lid of the bottle. This reservoir is opaque.
- the second (or dilutant) reservoir 524 namely the body of the bottle, comprises a chamber of dilutant (i.e. sterile pure water) at a pre-determined volume between 0.1 and 2 litres.
- the disinfectant reservoir 522 is separated from the dilutant reservoir 524 by a friable dispensing membrane 526.
- a friable dispensing membrane 526 There is also a second friable dispensing membrane 528 on the upper surface of the lid.
- a third (or indicator) reservoir could optionally be included, e.g. in the lid, above or below the disinfectant reservoir, separated from the adjacent reservoirs by additional friable membranes.
- the lid in dispensing mode the lid is removed and inverted on the bottle neck. This breaks both the friable members 526, 528.
- the membrane 526 separating the two reservoirs is broken first to allow the undiluted disinfectant solution to mix with the dilutant and thus the membrane 526 forms the disinfectant discharging means.
- the predetermined amount of undiluted disinfectant solution held in the disinfectant reservoir is wholly and completely discharged into the chamber (i.e. into the dilutant reservoir) which holds the predetermined amount of dilutant.
- the second membrane 528 is broken to allow the diluted disinfectant to be dispensed via a spout 530.
- mixing is a one-way, binary process.
- the opening of the device i.e. removal of the lid, causes mixing and thus the arrangement is such that mixing must occur before dispensing.
- the disinfectant reservoir has no direct access to the dispensing spout which reduces the chance of neat disinfectant being dispensed.
- FIGs 6a and 6b show a variant of the device 600 of Figure 5a .
- the device 600 is in the form of a bottle comprising two reservoirs (622 and 624).
- the first (or disinfectant) reservoir 622 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2 and is located in the lid of the bottle.
- the second (or dilutant) reservoir 624 namely the body of the bottle, comprises a chamber of dilutant.
- the disinfectant reservoir 622 is separated from the dilutant reservoir 624 by a friable dispensing membrane 626.
- a third (or indicator) reservoir could optionally be included, e.g. in the lid, above or below the disinfectant reservoir, separated from the adjacent reservoirs by additional friable membranes.
- the lid is not removed but simply screwed or pushed down further to activate the device.
- this example prevents neat dilutant and/or neat disinfectant being delivered because the lid is not removed until after mixing and there is no exposed friable membrane.
- the action of opening i.e. pushing down or twisting the bottle lid down, causes the lid to move down to first break the first membrane separating the reservoirs as shown in Figure 6b .
- the membrane 626 forms the disinfectant discharging means. Once the membrane 626 is broken, the predetermined amount of undiluted disinfectant solution held in the disinfectant reservoir is wholly and completely discharged into the chamber (i.e. into the dilutant reservoir) which holds the predetermined amount of dilutant.
- twisting to remove the lid causes the second membrane to be broken. Twisting the lid also moves paddle 630 which extends from the lid through the disinfectant reservoir and into the dilutant reservoir.
- the paddle 630 is an optional extra and stirs the newly mixed solution as the lid is twisted.
- the mixed solution may then be dispensed via the bottle's pump action dispenser (not shown) or another dispensing mechanism, e.g. squeeze bottle, pourer or even attached to a drip bag.
- the arrangement is such that mixing must occur before dispensing.
- the lid and/or bottle may have a visual indicator making it clear that the mixing has occurred, e.g. a coloured band on the bottle neck which is covered by the lid after mixing.
- FIGS 7a to 7e show a variant on the bottle device.
- the device 700 is in the form of a bottle comprising two reservoirs (722 and 724).
- the first (or disinfectant) reservoir 722 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2 and is located a bag within the bottle.
- the bag is suspended from the underside of the lid assembly.
- the second (or dilutant) reservoir 724 namely the body of the bottle, comprises a chamber of dilutant.
- the reservoirs are separated by a permanent barrier, namely the wall of the bag.
- a single plunger pump 730 located in the lid 731 is arranged to draw fluid from each reservoir simultaneously.
- the dilutant is drawn from the second reservoir 724 into an additional dilutant reservoir 726 via a tube 728.
- the undiluted disinfectant solution is drawn from the first reservoir through an orifice 731 into an additional disinfectant reservoir (outlet) 732.
- Both the additional dilutant reservoir and the additional disinfectant reservoir are in the form of annuli arranged concentrically around the pump action mechanism.
- the pump action mechanism comprises an upper plunger 740 mounted to a lower plunger 742 and a displacing protrusion 744.
- a pumping chamber 746 is formed between the lower surface of the upper plunger 740 and the upper surface of the displacing protrusion 744.
- the upper plunger comprises an exit passage 750 connected to a dispensing outlet 748 for dispensing dilute disinfectant.
- FIG. 7a to 7e The operation of the device is shown in Figures 7a to 7e .
- the system is at rest in Figure 7a with the pumping chamber 746 full of dilute disinfectant.
- Figure 7b shows the plunger partially depressed and shows the consequent reduction in the volume in the pumping chamber.
- Liquid is prevented from returning into the additional disinfectant or dilutant reservoirs by one-way discharging valve 752 and thus as shown by arrows
- a dilute disinfectant is forced through one-way exit valve 754 into the exit passage 750 and out from the dispensing outlet 748.
- Figure 7c shows the pumping chamber when it has been completed emptied.
- An elastomeric member 760 around the lower surface of the upper plunger limits the extent of the downward movement of the plunger and lessens any damage to the displacing protrusion.
- a spring (not shown) pushes the plunger back up.
- the pumping chamber now expands but the one-way exit valve 754 prevents air being drawn into the chamber.
- the pressure drop causes the one-way discharging valve 752 to open drawing undiluted disinfectant solution from the additional disinfectant reservoir 732 (arrow B) through an aperture 756 in the pumping chamber which may be termed the plunger entry orifice. Movement of the undiluted disinfectant solution from the additional reservoir to the pumping chamber, draws undiluted disinfectant solution from the disinfectant reservoir 722 into the additional disinfectant reservoir 732 (arrow C) as shown in Figure 7d .
- a ring 758 around the outer wall of the pumping chamber limits the extent of the upward movement of the plunger.
- the plunger continues to rise and draw in undiluted disinfectant solution until the aperture 756 is above the level of the additional disinfectant reservoir as shown in Figure 7e . Accordingly, during the portion of the stroke in which the aperture is aligned with the additional disinfectant reservoir, the predetermined amount of undiluted disinfectant solution is drawn into the pumping chamber. Thereafter fluid is drawn from the additional dilutant reservoir 726 (arrow D) through the aperture 756 in the pumping chamber. Movement of the dilutant from the additional reservoir to the pumping chamber, draws dilutant from the dilutant reservoir 724 into the additional disinfectant reservoir 726 (arrow E).
- the predetermined amount of dilutant is drawn into the pumping chamber.
- two or more pumps may be arranged to work synchronously, each one drawing fluid from each reservoir simultaneously.
- the drawn fluid passes into a common outlet or a set of closely spaced outlets.
- the ratio of the pumping volume per stroke sets the desired mixing ratio of the two fluids.
- the pumps are positive displacement plunger pumps.
- the arrangement of Figures 7a to 7e may comprise enough undiluted disinfectant solution and dilutant to provide more than one dose of dilute disinfectant.
- the size of the dose is determined by the size of the pumping chamber. Once the undiluted disinfectant solution and dilutant are exhausted, the bottle may be discarded.
- Figure 8 shows a device 800 in the form of a bag comprising two reservoirs (822 and 824).
- the first (or disinfectant) reservoir 822 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2.
- the second (or dilutant) reservoir 824 comprises dilutant.
- the reservoirs are separated by a thin friable membrane 826 which is torn by mechanically deforming the bag.
- the bag is made from a thicker and more durable material than the membrane so that it is not ruptured on deforming.
- the membrane 826 has a length shorter than the outer parts of the bag so that it can be broken by pulling the edges 828 of the bag in opposite directions as indicated by the arrows. Disruption of the membrane 826 causes fluid turbulence and hence mixing of the two components. Disruption of the membrane 826 also opens the dispensing aperture on the bag (not shown). As with other embodiments, the arrangement is such that mixing must occur before dispensing.
- the dispensing aperture is preferably located so that the disinfectant reservoir has no direct access to the dispensing aperture which reduces the chance of neat disinfectant being dispensed (e.g. located at one end of the dilutant reservoir).
- a third (or indicator) reservoir could optionally be included, e.g. by including an additional friable membrane above or below the membrane shown in Figure 8 , whereby the two membranes enclose the indicator reservoir.
- Figure 9 shows a device 900 in the form of a drip bag comprising two reservoirs (922 and 924).
- the first (or disinfectant) reservoir 922 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2.
- the second (or dilutant) reservoir 924 comprises dilutant.
- the reservoirs are separated by an external clip 926 that pinches the material of the bag along a line.
- the clip 926 also prevents dispensing of the contents because it pinches the tube connecting to the dispensing outlet 928.
- the clip is adapted, e.g. has a T-piece 930, to cause turbulence and promote fluid mixing.
- the clip may also only be slid off in one direction, i.e. over the outlet 928. In this way, no fluid escapes the device until mixing has occurred.
- the clip also preferably slides off over the disinfectant reservoir thus ensuring that the disinfectant can only be discharged via the mixing chamber, i.e. not neat.
- the outlet of the device is also disposed close to line dividing the two reservoirs so that the dispensed fluid is approximately of the correct concentration even if mixing is incomplete.
- a third (or indicator) reservoir could optionally be included, e.g. by dividing the disinfectant reservoir into two chambers, one holding undiluted disinfectant solution and one holding indicator. As the clip slides over the two chambers, the contents are discharged into the dilutant reservoir.
- Figure 10a shows a device 1000 in the form of a dual plunger comprising two reservoirs (1022 and 1024).
- the first (or disinfectant) reservoir 1022 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2.
- the second (or dilutant) reservoir 1024 comprises dilutant.
- the relative cross-sectional areas of the two reservoirs determines the mixing ratio.
- a roller 1026 is positioned at one end of the device and at the opposed end of the device both reservoirs have friable membranes 1028.
- the roller and the friable membranes cooperate to form the dilutant discharging means and the disinfectant discharging means.
- the dilutant and undiluted disinfectant solution are dispensed simultaneously by moving roller 1026 across the reservoirs which forces the liquids through the friable membranes 1028.
- dispensing is a one-way, binary process. The arrangement ensures that the liquids are dispensed simultaneously and will thus be in the correct concentration because of the relative cross-sectional areas of the two reservoirs.
- Figure 10b shows a device 1100 in the form of a syringe comprising two reservoirs (1122 and 1124).
- the first (or disinfectant) reservoir 1122 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2.
- the second (or dilutant) reservoir 1124 comprises dilutant.
- the relative volumes of the two reservoirs determines the mixing ratio.
- the two reservoirs are separated by the head 1128 of the syringe plunger.
- the head comprises either a one-way valve or a friable membrane 1126. Movement of the head away from the dispensing port 1130 causes the valve or membrane to open and mixing to occur. After mixing, the head is moved in the opposite direction to dispense the dilute disinfectant. There is a ratchet (not shown) to prevent movement of the head towards the outlet before mixing has occurred. Dispensing is a one-way, binary process, with mixing before dispensing and the only access for the disinfectant to the outlet is via the dilutant reservoir.
- Figure 11 shows a device 1120 in the form of a bottle comprising two reservoirs (1222 and 1224).
- the first (or disinfectant) reservoir 1222 comprises 1% or 2% stabilised sodium hypochlorite solution as per the formulation of Milton 1 or Milton 2 and is in the form of a blister pack on the side of the bottle.
- the second (or dilutant) reservoir 1224 comprises dilutant and is the body of the bottle. The relative volumes of the two reservoirs determines the mixing ratio. Dispensing is a one-way, binary process with mixing before dispensing and the only access for the disinfectant to the outlet is via the dilutant reservoir.
- the two reservoirs are separated by a friable inner membrane positioned over a hole in the bottle wall.
- the inner membrane is broken by pressing on the blister.
- a dye may be used to colour the disinfectant in the blister so that it is obvious when mixing has occurred.
- a second blister pack could be mounted on the bottle to form a third (disinfectant reservoir).
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1006187.7A GB201006187D0 (en) | 2010-04-14 | 2010-04-14 | Device for preparing dilute disinfectant solution |
GBGB1102135.9A GB201102135D0 (en) | 2011-02-08 | 2011-02-08 | Device for preparing dilute disinfectant solution |
PCT/GB2011/050729 WO2011128682A2 (en) | 2010-04-14 | 2011-04-13 | Device for preparing dilute disinfectant solution |
Publications (2)
Publication Number | Publication Date |
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EP2558156A2 EP2558156A2 (en) | 2013-02-20 |
EP2558156B1 true EP2558156B1 (en) | 2017-11-01 |
Family
ID=44799092
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP11716993.8A Active EP2558156B1 (en) | 2010-04-14 | 2011-04-13 | Device for preparing dilute disinfectant solution |
Country Status (9)
Country | Link |
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US (2) | US9492352B2 (zh) |
EP (1) | EP2558156B1 (zh) |
JP (2) | JP5951596B2 (zh) |
KR (1) | KR20130092977A (zh) |
CN (1) | CN102939130A (zh) |
CA (1) | CA2796029A1 (zh) |
ES (1) | ES2656825T3 (zh) |
IL (1) | IL222380A (zh) |
WO (1) | WO2011128682A2 (zh) |
Cited By (1)
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WO2024123498A1 (en) * | 2022-12-05 | 2024-06-13 | The Clorox Company | Stable hypohalite concentrate and dilution system |
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WO2011128682A2 (en) | 2010-04-14 | 2011-10-20 | Hypo-Stream Limited | Device for preparing dilute disinfectant solution |
US20140271925A1 (en) * | 2013-03-13 | 2014-09-18 | NEET Innovations, LLC | Modulating surface and aerosol iodine disinfectant system |
GB2527264A (en) * | 2014-01-23 | 2015-12-23 | Hypo Stream Ltd | Anti-inflammatory solution |
CN105848660A (zh) * | 2013-10-29 | 2016-08-10 | 海波流动有限公司 | 包含次氯酸钠的抗炎溶液 |
DE102015218040A1 (de) * | 2015-09-21 | 2017-03-23 | Robert Hellmundt | Desinfektionsmittelspender zur Bevorratung und Entnahme eines Mittels zur Oberflächen- und/oder Hautdesinfektion, Desinfektionsmittel und Verfahren zur öffentlichen Signalisierung eines Desinfektionszustandes von Personen |
HUP1600669A2 (en) * | 2016-12-14 | 2018-06-28 | Handinscan Zrt | Method, apparatus and computer program product for hand disinfection quality control |
IT201800001927A1 (it) * | 2018-01-26 | 2019-07-26 | Ripantiripanti Tiziano | Struttura di accessorio per macchina da tatuaggi |
KR20220084109A (ko) * | 2019-11-11 | 2022-06-21 | 프로그래스 가부시키가이샤 | 항암제 노출 방지 방법 |
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2011
- 2011-04-13 WO PCT/GB2011/050729 patent/WO2011128682A2/en active Application Filing
- 2011-04-13 JP JP2013504342A patent/JP5951596B2/ja active Active
- 2011-04-13 CA CA2796029A patent/CA2796029A1/en not_active Abandoned
- 2011-04-13 KR KR1020127029879A patent/KR20130092977A/ko not_active Application Discontinuation
- 2011-04-13 EP EP11716993.8A patent/EP2558156B1/en active Active
- 2011-04-13 US US13/639,224 patent/US9492352B2/en active Active
- 2011-04-13 CN CN2011800290314A patent/CN102939130A/zh active Pending
- 2011-04-13 ES ES11716993.8T patent/ES2656825T3/es active Active
-
2012
- 2012-10-11 IL IL222380A patent/IL222380A/en not_active IP Right Cessation
-
2016
- 2016-03-01 JP JP2016038963A patent/JP2016163886A/ja not_active Ceased
- 2016-10-05 US US15/286,504 patent/US10188111B2/en active Active
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2024123498A1 (en) * | 2022-12-05 | 2024-06-13 | The Clorox Company | Stable hypohalite concentrate and dilution system |
Also Published As
Publication number | Publication date |
---|---|
EP2558156A2 (en) | 2013-02-20 |
JP5951596B2 (ja) | 2016-07-13 |
ES2656825T3 (es) | 2018-02-28 |
IL222380A0 (en) | 2012-12-31 |
JP2016163886A (ja) | 2016-09-08 |
US20170020135A1 (en) | 2017-01-26 |
US20130072867A1 (en) | 2013-03-21 |
US9492352B2 (en) | 2016-11-15 |
KR20130092977A (ko) | 2013-08-21 |
US10188111B2 (en) | 2019-01-29 |
WO2011128682A3 (en) | 2012-01-19 |
IL222380A (en) | 2016-02-29 |
JP2013529125A (ja) | 2013-07-18 |
CN102939130A (zh) | 2013-02-20 |
WO2011128682A2 (en) | 2011-10-20 |
CA2796029A1 (en) | 2011-10-20 |
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